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Obsessive-compulsive disorder (OCD) is a common psychiatric condition classically characterized by obsessions (recurrent, intrusive and unwanted thoughts) and compulsions (excessive, repetitive and ritualistic behaviors or mental acts). OCD is heterogeneous in its clinical presentation and not all patients respond to first-line treatments. Several neurocircuit models of OCD have been proposed with the aim of providing a better understanding of the neural and cognitive mechanisms involved in the disorder. These models use advances in neuroscience and findings from neuropsychological and neuroimaging studies to suggest links between clinical profiles that reflect the symptoms and experiences of patients and dysfunctions in specific neurocircuits. Several models propose that treatments for OCD could be improved if directed to specific neurocircuit dysfunctions, thereby restoring efficient neurocognitive function and ameliorating the symptomatology of each associated clinical profile. Yet, there are several important limitations to neurocircuit models of OCD. The purpose of the current review is to highlight some of these limitations, including issues related to the complexity of brain and cognitive function, the clinical presentation and course of OCD, etiological factors, and treatment methods proposed by the models. We also provide suggestions for future research to advance neurocircuit models of OCD and facilitate translation to clinical application.

https://doi.org/10.1590/1516-4446-2020-1709

Precision non-implantable neuromodulation therapies: a perspective for the depressed brain
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Borrione, Lucas

; Bellini, Helena

; Razza, Lais Boralli

; Avila, Ana G.

; Baeken, Chris

; Brem, Anna-Katharine

; Busatto, Geraldo

; Carvalho, Andre F.

; Chekroud, Adam

; Daskalakis, Zafiris J.

; Deng, Zhi-De

; Downar, Jonathan

; Gattaz, Wagner

; Loo, Colleen

; Lotufo, Paulo A.

; Martin, Maria da Graça M.

; McClintock, Shawn M.

; O’Shea, Jacinta

; Padberg, Frank

; Passos, Ives C.

; Salum, Giovanni A.

; Vanderhasselt, Marie-Anne

; Fraguas, Renerio

; Benseñor, Isabela

; Valiengo, Leandro

; Brunoni, Andre R.

Brazilian Journal of Psychiatry

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Ago 2020, Volume 42 Nº 4 Páginas 403 - 419

Resumo: En | Texto: En | PDF: En

Current first-line treatments for major depressive disorder (MDD) include pharmacotherapy and cognitive-behavioral therapy. However, one-third of depressed patients do not achieve remission after multiple medication trials, and psychotherapy can be costly and time-consuming. Although non-implantable neuromodulation (NIN) techniques such as transcranial magnetic stimulation, transcranial direct current stimulation, electroconvulsive therapy, and magnetic seizure therapy are gaining momentum for treating MDD, the efficacy of non-convulsive techniques is still modest, whereas use of convulsive modalities is limited by their cognitive side effects. In this context, we propose that NIN techniques could benefit from a precision-oriented approach. In this review, we discuss the challenges and opportunities in implementing such a framework, focusing on enhancing NIN effects via a combination of individualized cognitive interventions, using closed-loop approaches, identifying multimodal biomarkers, using computer electric field modeling to guide targeting and quantify dosage, and using machine learning algorithms to integrate data collected at multiple biological levels and identify clinical responders. Though promising, this framework is currently limited, as previous studies have employed small samples and did not sufficiently explore pathophysiological mechanisms associated with NIN response and side effects. Moreover, cost-effectiveness analyses have not been performed. Nevertheless, further advancements in clinical trials of NIN could shift the field toward a more “precision-oriented” practice.

https://doi.org/10.1590/1516-4446-2019-0741 1546 downloads

Association of BDNF, HTR2A, TPH1, SLC6A4, and COMT polymorphisms with tDCS and escitalopram efficacy: ancillary analysis of a double-blind, placebo-controlled trial
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Brunoni, Andre R.

; Carracedo, Angel

; Amigo, Olalla M.

; Pellicer, Ana L.

; Talib, Leda

; Carvalho, Andre F.

; Lotufo, Paulo A.

; Benseñor, Isabela M.

; Gattaz, Wagner

; Cappi, Carolina

Brazilian Journal of Psychiatry

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Abr 2020, Volume 42 Nº 2 Páginas 128 - 135

Resumo: En | Texto: En | PDF: En

Objective: We investigated whether single nucleotide polymorphisms (SNPs) associated with neuroplasticity and activity of monoamine neurotransmitters, such as the brain-derived neurotrophic factor (BDNF, rs6265), the serotonin transporter (SLC6A4, rs25531), the tryptophan hydroxylase 1 (TPH1, rs1800532), the 5-hydroxytryptamine receptor 2A (HTR2A, rs6311, rs6313, rs7997012), and the catechol-O-methyltransferase (COMT, rs4680) genes, are associated with efficacy of transcranial direct current stimulation (tDCS) in major depression. Methods: Data from the Escitalopram vs. Electrical Current Therapy for Treating Depression Clinical Study (ELECT-TDCS) were used. Participants were antidepressant-free at baseline and presented with an acute, moderate-to-severe unipolar depressive episode. They were randomized to receive escitalopram/tDCS-sham (n=75), tDCS/placebo-pill (n=75), or placebo-pill/sham-tDCS (n=45). General linear models assessed the interaction between treatment group and allele-wise carriers. Additional analyses were performed for each group and each genotype separately. Results: Pairwise group comparisons (tDCS vs. placebo, tDCS vs. escitalopram, and escitalopram vs. placebo) did not identify alleles associated with depression improvement. In addition, exploratory analyses also did not identify any SNP unequivocally associated with improvement of depression in any treatment group. Conclusion: Larger, combined datasets are necessary to identify candidate genes for tDCS response.

https://doi.org/10.1590/1516-4446-2019-0620 1172 downloads

Precision noninvasive brain stimulation: is it precise? Is it needed?
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Borrione, Lucas

; Brunoni, Andre R.

Brazilian Journal of Psychiatry

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Out 2019, Volume 41 Nº 5 Páginas 376 - 377

Resumo: En | Texto: En | PDF: En

https://doi.org/10.1590/1516-4446-2019-4110 531 downloads

Epidemiological research in psychiatry: acting glocally
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Fidalgo, Thiago M.

; Brunoni, Andre R.

Brazilian Journal of Psychiatry

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Abr 2019, Volume 41 Nº 2 Páginas 99 - 100

Resumo: En | Texto: En | PDF: En

https://doi.org/10.1590/1516-4446-2019-4102 1039 downloads

Noninvasive brain stimulation in psychiatric disorders: a primer
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Brunoni, Andre R.

; Sampaio-Junior, Bernardo

; Moffa, Adriano H.

; Aparício, Luana V.

; Gordon, Pedro

; Klein, Izio

; Rios, Rosa M.

; Razza, Lais B.

; Loo, Colleen

; Padberg, Frank

; Valiengo, Leandro

Brazilian Journal of Psychiatry

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Fev 2019, Volume 41 Nº 1 Páginas 70 - 81

Resumo: En | Texto: En | PDF: En

Objective: Noninvasive brain stimulation (NIBS) techniques, such as transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS), are increasingly being used to treat mental disorders, particularly major depression. The aim of this comprehensive review is to summarize the main advances, limitations, and perspectives of the field. Methods: We searched PubMed and other databases from inception to July 2017 for articles, particularly systematic reviews and meta-analyses, evaluating the use of NIBS in psychiatric disorders. Results: We reviewed the mechanisms of action, safety, tolerability, efficacy, and relevant clinical parameters of NIBS. Repetitive TMS is already an established technique for the treatment of depression, and there is theoretically room for further methodological development towards a high-end therapeutic intervention. In contrast, tDCS is a technically easier method and therefore potentially suitable for wider clinical use. However the evidence of its antidepressant efficacy is less sound, and a recent study found tDCS to be inferior to antidepressant pharmacotherapy. Clinical trials using rTMS for other mental disorders produced mixed findings, whereas tDCS use has not been sufficiently appraised. Conclusion: The most promising results of NIBS have been obtained for depression. These techniques excel in safety and tolerability, although their efficacy still warrants improvement.

https://doi.org/10.1590/1516-4446-2017-0018 3378 downloads

A call to action for publishing study designs and preliminary results in the Archives of Clinical Psychiatry
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Brunoni, Andre R.

Archives of Clinical Psychiatry (São Paulo)

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Dez 2018, Volume 45 Nº 6 Páginas 137 - 138

Resumo: En | Texto: En | PDF: En

https://doi.org/10.1590/0101-60830000000175 729 downloads

10.

Early psychiatric morbidity in a Brazilian sample of acute ischemic stroke patients
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Pedroso, Vinicius S.P.

; Brunoni, Andre R.

; Vieira, Érica L.M.

; Jorge, Ricardo E.

; Lauterbach, Edward C.

; Teixeira, Antonio L.

Clinics

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2018, Volume 73 elocation e55

Resumo: En | Texto: En | PDF: En

OBJECTIVE: Stroke is a major public health problem worldwide, and its neuropsychiatric sequelae are frequent and disabling. Furthermore, there is evidence that these sequelae impair recovery. Brazil has the highest stroke rates in Latin America, but data on the frequency of neuropsychiatric disorders in these patients are scarce. This study aimed to identify mental disorders among in-hospital patients with acute ischemic stroke. METHODS: The Mini International Neuropsychiatric Interview-Plus (MINI-Plus) was applied to 60 patients during the first week of hospitalization. RESULTS: Psychiatric disorders were diagnosed in 55% of the patients. A wide range of neuropsychiatric disorders have been identified, mainly mood and anxiety disorders. Specifically, we identified major depression (26.7%), alcohol abuse or dependence (11.7%), specific phobia (8.3%), generalized anxiety disorder (6.7%), psychosis (5.0%), social phobia (3.3%), adjustment disorder (3.3%) and panic disorder (1.7%). CONCLUSION: Psychiatric comorbidity should be evaluated as part of the rehabilitation of stroke patients and should be carefully examined by physicians.

https://doi.org/10.6061/clinics/2018/e055 906 downloads

11.

Primum non nocere or primum facere meliorem? Hacking the brain in the 21st century
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Borrione, Lucas

; Brunoni, Andre R.

Trends in Psychiatry and Psychotherapy

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Dez 2017, Volume 39 Nº 4 Páginas 232 - 238

Resumo: Pt En | Texto: Pt En | PDF: Pt | PDF: En

Resumo A estimulação transcraniana por corrente contínua (ETCC) é uma técnica não invasiva de estimulação cerebral que modula a excitabilidade cortical. A ETCC é desprovida de efeitos adversos graves e exerce efeitos variáveis sobre a cognição, com vários achados de pesquisa sugerindo que a técnica pode promover melhora nas habilidades mnêmica, verbal e matemática. Devido ao seu baixo custo, portabilidade e facilidade de montagem, os aparelhos de ETCC tornaram-se disponíveis fora do contexto médico, sendo usados para fins não médicos (“cosméticos”) por indivíduos leigos. Nesse sentido, a ETCC tornou-se um procedimento popular para aprimoramento da cognição e a realização de melhor desempenho não somente no ambiente de trabalho, mas também em campos tais como o esporte, atividades de lazer ( video games ) e até no meio militar. Apesar desses acontecimentos imprevisíveis, há uma certa morosidade das agências médicas e regulatórias em desenvolver diretrizes para o uso de ETCC para fins cosméticos. Há muitos desafios presentes, principalmente, como restringir o uso da ETCC fora do contexto médico em face de resultados variáveis, e muitas vezes conflitantes, da pesquisa científica sobre o tema. Este artigo tem como objetivo descrever o uso popular da ETCC sob a luz da neuroética, um ramo da bioética que se dedica ao estudo do cérebro. Entre duas situações possíveis, mas extremas – liberação ou restrição totais da ETCC –, é primordial o desenvolvimento de um espectro de alternativas, que podem variar ao longo do tempo e depender de diversos contextos culturais.

Abstract Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that modulates cortical excitability. It is devoid of serious adverse events and exerts variable effects on cognition, with several research findings suggesting that it can improve memory, verbal and mathematical skills. Because tDCS devices are low-cost, portable and relatively easy to assemble, they have become available outside of the medical setting and used for non-medical (“cosmetic”) purposes by laypersons. In this sense, tDCS has become a popular technique aiming to improve cognition and the achievement of a better performance not only at work, but also in other fields such as sports, leisure activities (video games) and even the military. In spite of these unforeseen developments, there has been a general paralysis of the medical and regulatory agencies to develop guidelines for the use of tDCS for cosmetic purposes. Several challenges are present, most importantly, how to restrict tDCS use outside of the medical setting in face of variable and sometimes conflicting results from scientific research. This article aims to describe the popular use of tDCS, in light of the pillars of neuroethics, a branch of bioethics relative to brain research. Between two possible but extreme solutions – total release or total restriction of tDCS – it is paramount to develop a spectrum of alternatives, which may vary over time and in different cultural backgrounds.

https://doi.org/10.1590/2237-6089-2017-0075 1443 downloads

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Post stroke depression: clinics, etiopathogenesis and therapeutics
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PEDROSO, VINICIUS SOUSA PIETRA

; SOUZA, LEONARDO CRUZ

; BRUNONI, ANDRE R

; TEIXEIRA, ANTÔNIO LÚCIO

Archives of Clinical Psychiatry (São Paulo)

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Fev 2015, Volume 42 Nº 1 Páginas 18 - 24

Resumo: En | Texto: En | PDF: En

Background Stroke is a major cause of morbidity and mortality worldwide. Neuropsychiatric disorders are often associated with stroke and, among them, depression is the most prevalent. Post-stroke Depression (PSD) is related to disability, failure in returning to work, impairment in interpersonal functioning and mortality. Its etiopathogenesis is still uncertain, as well as its treatment. In Brazil, there are few data on the impact of PSD. Objective This work is dedicated to conduct a comprehensive review of the concept of PSD, its pathophysiology, morbidity and treatment. Methods PubMed, Medline and Lilacs searches of relevant terms yielded 3,265 papers in the last 10 years. We selected original studies and reviews that addressed the aspects mentioned above. Results We present the history of the notion of PSD and describe its epidemiology, looking to highlight Brazilian studies. Diagnostic criteria and clinical presentation were detailed, with emphasis on cognitive aspects. The four main pathophysiological theories proposed to PSD are presented and we discuss the various treatment strategies, involving psychopharmacologic options, brain stimulation techniques and psychotherapy. Discussion This work provides comprehensive information on PSD, of great utility for clinical practice and research in this topic.

https://doi.org/10.1590/0101-60830000000041 5811 downloads

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